Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos

• Published in: Stem cell reports Vol. 9; no. 5; pp. 1387 - 1394
• Main Authors: Jennings, Rachel E., Berry, Andrew A., Gerrard, David T., Wearne, Stephen J., Strutt, James, Withey, Sarah, Chhatriwala, Mariya, Piper Hanley, Karen, Vallier, Ludovic, Bobola, Nicoletta, Hanley, Neil A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.11.2017; Elsevier
• Subjects: Cell Differentiation; development; embryo; Gene Expression Profiling; Gene Expression Regulation, Developmental; human; Human Embryonic Stem Cells - cytology; Human Embryonic Stem Cells - metabolism; Humans; liver; Liver - embryology; Liver - metabolism; pancreas; Pancreas - embryology; Pancreas - metabolism; RNA sequencing; stem cell; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Activation; Transcriptome; RNA sequencing; development; stem cell; liver; pancreas; transcriptome; embryo; human
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2017.09.018

To interrogate the alternative fates of pancreas and liver in the earliest stages of human organogenesis, we developed laser capture, RNA amplification, and computational analysis of deep sequencing. Pancreas-enriched gene expression was less conserved between human and mouse than for liver. The dorsal pancreatic bud was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored transcription factors. SOX9 and RORA were imputed as key regulators in pancreas compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied that current in vitro human stem cell differentiation follows a dorsal rather than a ventral pancreatic program and pointed to additional factors for hepatic differentiation. In summary, we provide the transcriptional codes regulating the start of human liver and pancreas development to facilitate stem cell research and clinical interpretation without inter-species extrapolation. [Display omitted] •Transcriptomic signatures at the inception of human liver and pancreas development•Limited conservation of pancreas-enriched gene expression between human and mouse•Human PSC protocols imply a dorsal rather than a ventral pancreatic program•New pancreatic transcription factors imputed by differential analysis Jennings et al. present the first transcriptomes at the inception of liver and pancreas development in very early post-implantation human embryos. By computational analysis, they impute regulatory signatures in each organ, including new transcription factors in pancreas and new guidance for human pluripotent stem cell differentiation.